This application claims priority to U.S. Ser. No. 60/590,400 filed Jul. 22, 2004.
The present invention is generally in the field of diagnosing areas in the body that contain antigenic, diseased, transformed or neoplastic tissue that is associated with an inflammatory response. This is accomplished by the administration and imaging of radiolabelled antibodies to tumor necrosis factor receptor. This diagnostic test is intended for early diagnosis of disease in mammals.
The two main causes of death in this country are heart disease and cancer. Researchers today are finding more and more evidence that these diseases start with an inflammatory response involving the immune system. The various response organs, such as the gut, skin, lungs, bone marrow, thymus, and spleen, react with the production of special messenger substances that activate/create macrophages, T-cells, B-cells and NK-cells, all with specific functions to protect the body from invasion of other living organisms as well as toxins. Some of these messenger substances include cytokines such as TNF and C-reactive protein, lymphotoxins, and leukotrienes.
Tumor Necrosis Factor (TNF) is a pirotrophic pro-inflammatory cytokine produced by macrophages. The amount of TNF is crucial; too much can cause cachexia and septic shock, while too little can allow infection and cancer. The body's white cells will recognize a cancer cell, bind to it (if not blocked/inhibited) and kill it with TNF. This reaction is inhibited by immunosuppressants, either from outside the body (medications, radiation, environmental toxins) or from within (tumor production of cell surface TNF receptors (sTNF-R1 and sTNF-R2). If the inhibitors/blockers of the normal white cell response can be removed, then the immune system can attack and kill the affected cells.
The TNF receptors (sTNF-R1 and sTNF-R2) are present on all mammalian cells. Over production and shedding of these receptors into body fluids causal to acquired immune tolerance. These soluble shed receptors are found in increased quantities in the immediate cellular microenvironment of antigenic tissues and cells. (Lentz M R. The phylogeny of oncology. Mol Biotherm. 2:137-144 (1990)). The result of this over-production and shedding is to protect the antigenic cell or an antigen from an otherwise normal inflammatory/immune response.
The most crucial aspect in the successful treatment of any cancer is early detection. Likewise, it is crucial to properly diagnose chronic and acute inflammatory conditions, i.e, autoimmune diseases, before tissue and organ destruction occurs. PET, MRI, and CT scans are limited in their sensitivity.
It is therefore an object of the present invention to provide a method and system for early detection of tumors and other types of diseased tissue.